Cellular adaptations and injury

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Cellular adaptations and injury

• BIOL 460
• Walter L. Kemp, MD
• Deputy State Medical Examiner
• Montana State, Forensic Science Division
• Clinical Assistant Professor
• University of Texas Southwestern
• wkemp_at_mt.gov 329-1178

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What is cellular adaptation?

• Cellular adaptation is the bodys method for
  dealing with stressors (both physiologic and
  pathologic) to maintain homeostasis
• If the stressor is removed, all forms of
  adaptation (hyperplasia, hypertrophy, atrophy and
  metaplasia) are potentially reversible however,
  the stressor must be identified and removed
• Eventually, if the stressor is severe enough,
  adaptation will fail and organ injury (cell
  death) occurs

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Cellular adaptation

• Hyperplasia
• An organized increase in number of cells (versus
  dysplasia, which is disorganized growth, and
  neoplasia, which is new growth).
• Can be physiologic or pathologic
• Hypertrophy
• An increase in cell size
• Can be physiologic or pathologic

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Cellular adaptation (cont)

• Hyperplasia and hypertrophy can be difficult to
  separate--not possible by gross exam difficult
  by microscopic exam. In some cases, both
  hyperplasia and hypertrophy occur together (e.g.,
  breast and uterus during pregnancy).
• Hyperplasia essentially does not occur in the
  brain and heart

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Cellular adaptation (cont)

• Atrophy
• Decrease in cell size
• Can be physiologic or pathologic
• Metaplasia Change in type of epithelium (e.g.,
  squamous epithelium to glandular epithelium)

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Hyperplasia

• Physiologic
• Breast enlargement during pregnancy (and
  hypertrophy)
• Uterine enlargement during pregnancy (and
  hypertrophy)
• Liver regrowth after partial resection
• Inflammation, repair
• Pathologic
• Ductal hyperplasia of breast (due to estrogen)
• Benign prostatic hyperplasia
• Endometrial hyperplasia (due to estrogen)
• Viral infections
• Endocrine organs with increased stimulus (e.g.,
  adrenal gland enlargement due to ACTH-secreting
  pituitary adenoma goiter)

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Hypertrophy

• Physiologic
• Skeletal muscle hypertrophy associated with
  exercise
• Compensatory hypertrophy of kidney after removal
  of other kidney
• Pathologic
• Cardiac hypertrophy due to hypertension, valvular
  stenosis or insufficiency
• Asthma--smooth muscle hypertrophy
• Hypertrophy of bladder associated with prostatic
  gland hyperplasia

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Atrophy

• Physiologic
• Regression in size of breasts and uterus after
  pregnancy
• Pathologic
• Disuse (skeletal muscle atrophy)
• Loss of endocrine stimulus (adrenal atrophy in
  patients on steroids)
• Denervation (physical therapists vs forensic
  pathologists)
• Inadequate nutrition
• Ischemia (atrophy of kidney due to renal artery
  stenosis)

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Metaplasia

• Always pathologic
• Examples
• Squamous metaplasia of the lungs
• Glandular metaplasia of the esophagus (Barrett
  esophagus)

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Cellular accumulations

• Lipofuscin
• Calcium
• Fat
• Iron
• Protein, cholesterol, glycogen
• Pigments
• Exogenous Anthracosis, tattoos
• Endogenous Bile, melanin

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Why do cells accumulate substances?

• Too much produced
• Too slow of clearance
• Lack of enzyme decreased enzyme activity
• Blockage of outlet
• Cellular accumulations are a sign of injury
  cellular accumulations result from injury, or,
  their accumulation can cause cellular injury

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Common locations of various cellular accumulations

• Lipofuscin (wear and tear pigment)
• Heart, liver
• Fat
• Liver, heart, kidney
• Iron
• Lung (in patients with congestive heart failure)
• At site of past hemorrhage
• In patients with hemochromatosis
• Liver, heart, pancreas
• Cholesterol

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Protein accumulation

• Alzheimer disease (tau protein)
• Mallory hyaline (intermediate filaments in
  alcoholic liver disease)
• In kidney (as result of proteinuria)

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Pigments

• Endogenous
• Bilirubin, melanin
• Accumulation of bilirubin
• Too much produced (e.g., hemolysis)
• Not processed (e.g., cirrhosis)
• Outflow blocked (e.g. choledocholithiasis)
• Exogenous
• Anthracosis (cigarette smoking urban living)
• Tattoo

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Calcification

• Dystrophic
• Patients have a normal calcium level
• Calcification affects previously damaged tissue
• Metastatic
• Patients have an elevated level of calcium
• Causes Hyperparathyroidism, bony metastases
• Calcification affects normal tissue and
  previously damaged tissue
• Out of all forms of cellular adaptation,
  calcification is the only one which is not
  routinely reversible

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Dysplasia

• Definition Disorganized growth hyperplasia
  leads to dysplasia which leads to neoplasia
• Importance Precursor of malignancy but is
  reversible
• Common locations
• Cervix
• Gastrointestinal tract
• Not commonly seen by forensic pathologists

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Cell injury

• Causes hypoxia, ischemia, trauma, infections,
  autoimmune, toxins, immune conditions
• Cell injury leading to cell death
• DNA
• Cell membranes (plasma and lysosomal)
• Protein generation
• ATP production

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Cell injuryReversible and irreversible

• Reversible
• Cellular swelling can be reversed if Na/K pump
  starts working again
• pH can be reversed if aerobic respiration starts
• Irreversible injury
• Damage to plasma or lysosomal membranes, loss of
  DNA, loss of mitochondria will cause death of cell

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Necrosis

• Definition Morphologic cell death
• Variants
• Coagulative necrosis (protein denaturationgtenzymat
  ic breakdown)
• Liquefactive necrosis (enzymatic
  breakdowngtprotein denaturation)
• Fat necrosis, caseous necrosis, gangrenous
  necrosis (wet and dry)

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Cellular adaptations commonly/uncommonly seen by
forensic pathologists (biased)

• Hyperplasia
• Benign prostatic hyperplasia (uncommon)
• Adrenal gland hyperplasia (common to uncommon)
• Hypertrophy
• Cardiac (common)
• Atrophy
• Metaplasia
• Squamous metaplasia of lung and Barrett esophagus
  (uncommon)

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Cellular adaptations commonly/uncommonly seen by
forensic pathologists (cont)

• Fat
• Hepatic steatosis (common)
• Iron
• Congestive heart failure sites of hemorrhage
  (common)
• Hereditary hemochromatosis is rarely seen
• Protein accumulation
• Mallory hyaline (uncommon)
• Tangles and plaques in Alzheimer dz (uncommon)
• Cholesterol
• Atherosclerosis (common)

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Cellular adaptations commonly/uncommonly seen by
forensic pathologists

• Pigments
• Anthracosis (common)
• Bile (uncommon)
• Calcification
• Atherosclerosis (common)
• Aortic stenosis (uncommon)